The purpose of this project is the determination of the physicochemical properties of polymers of sickle cell hemoglobin (Hb S) when deoxygenated, since such polymers and their alignment into regular arrays are the putative cause of the sickling phenomenon. Knowledge of the intermolecular interactions within the polymeric microtubular structure of deoxy-Hb S could lead to a rational, rather than an empirical therapy for sickle cell anemia. X-ray diffraction studies using isomorphous replacement methods should give information from which the surface lattice of the microtubules can be established. The molecular orientation in the microtubular structure can then be found by application of molecular replacement techniques. From these results, the regions of contact between neighboring molecules in the microtubule can be identified. The participation of other hemoglobins, Hb X, in the deoxy-Hb S polymer will be investigated inasmuch as such non-S hemoglobins occur in erythrocytes of heterozygotes. The contribution of Hb X to diffraction patterns of microtubules, the solubility of binary mixtures of deoxy Hb-S and Hb X, and the concentration of Hb X in monomeric solution in equilibrium with polymers will be determined. An understanding of the state of hemoglobin in the sickled erythrocyte should evolve from this information. BIBLIOGRAPHIC REFERENCE: Thermodynamic studies of polymerization of deoxygenated sickle cell hemoglobin. Proc. Nat. Acad. Sci. USA, (1976) 73:990-994 by Beatrice Magdoff-Fairchild, William N. Poillon, Ting-I Li, and John F. Bertles.